Glucose, in addition to its central role in metabolism, also plays an important role as a signaling molecule in animal and plant cells. Glucose sensing is critical to such diverse physiological phenomena as regulation of metabolism in yeast, photosynthesis in higher plants, and, in mammals, the regulation of food intake, blood glucose levels, and enteric reflexes. Apart from yeast, where homologs of facilitated glucose transporters (Snf3 and Rgt2) have been implicated in glucose sensing, little is known about the molecular mechanisms involved.
A family of proteins that are reported to act as transporters have been described. Human members of the SLC5 gene family include the intestinal and renal glucose transporters (SLC5A1, SLC5A2), the widely distributed inositol and multivitamin transporters (SLC5A3, SLC5A6) and the thyroid iodide transporter (SLC5A5). While a major function of these plasma membrane proteins is secondary active transport in epithelia, they also behave as Na+ uniporters, water and urea channels, and water cotransporters.
A pig SGLT3 expressed in Xenopus leavis oocytes behaves as tightly coupled Na+/glucose cotransporter with a lower affinity for glucose and a more restricted sugar specificity than SGLT1 (SLC5A1) clones. The human homolog to pig SGLT3 (hSGLT3, SLC5A4) was identified in the sequencing of chromosome 22. The sequence of the human protein and gene may be accessed at Genbank, NM—014227.
In view of the importance of glucose sensing in food intake, digestion, blood glucose levels, and enteric reflexes, the expression of such sensors is of great interest. The identification and isolation of sensing receptors (including ion channels), and signaling molecules would allow for the pharmacological and genetic modulation of these pathways. For example, availability of sensor and channel molecules would permit the screening for high affinity agonists, antagonists, inverse agonists, and modulators of activity. Such compounds could then be used in the pharmaceutical and food industries.